As a result of many ocular disorders and injuries, bleeding into the vitreous may occur. An hemorrhagic event may elicit a series of pathological changes as the vitreous responds to injury. This proposal aims to examine alterations in vitreous cell populations, connective tissue proteins and physical structure following the intravitreal introduction in the rabbit of hemoglobin, a major injurious agent in blood. Microscopical examination of the changes with time after experimental hemorrhage in vitreal cell number and type are proposed. Further, the role of proliferation of cells in, and adjacent to, the vitreous will be investigated by radioautography. A serious potential consequence of vitreous hemorrhage is the formation of fibrous strands with attendant contraction and possible retinal detachment. The formation of fibrous strands may be associated with an altered collagen metabolism coupled with a compromise of the normal vitreous connective tissue feltwork. Biochemical analyses of collagen synthesis and breakdown are proposed. Of particular interest is the question of changes in the amount and type of collagen that may be deposited after injury since the vitreous requires a particular organization for its clarity. In addition to new synthesis, the proposal aims to examine the degradation of the existing matrix which may occur by the action of oxygen free radicals, changes in the enzymatic environment, or both. In this regard, levels of free radical scavengers (especially superoxide dismutase) will be investigated with an end to determine not only endogenous changes, but also the therapeutic efficacy of these agents in preventing damaging vitreous modifications. The overall goal of this proposal is to provide a multidisciplinary approach to understanding concurrent changes in the total vitreous environment after hemorrhagic injury. This information is essential to ascertaining those agents which may interrupt a pathological progression of events.